Light source

ABSTRACT

A cosmetic method of treatment of dermatological conditions, particularly portwine stains, tattoos or psoriasis, which includes irradiating the affected area with an incoherent high intensity non-laser light beam having an intensity greater than 0.075 watts per square centimeter, the light beam having only a bandwidth in the range 0 to 30 nm. The method can include delivery of the light beam by optic fiber bundle by pulsed or non-pulsed light. The method can also include the introduction of a drug into the body undergoing the treatment, wherein the drug is activated by light of a particular wavelength.

This is a division of application Ser. No. 08/256,059, filed Aug. 24,1994.

This invention relates to a light source which is an incoherent ornon-laser light source for use primarily but not exclusively in medicalapplications.

Lasers have widespread uses in the treatment of the human or animalbody, which uses may be of a therapeutic and/or cosmetic nature. Forexample, laser light can be used to kill cancer cells or for treatmentof portwine stains and removal of tattoos. However, medical lasers tendto have many disadvantages. Firstly, some medical lasers for certainrequirements can cost up to a one hundred and forty thousand pounds ormore and may require very bulky power supplies and/or bulky transformersin addition to involving complex or inconvenient cooling arrangements.Additionally, the power consumption by the laser may be very high andthe laser itself may not be user friendly, for example, some lasers mayrequire a one and a half hour warm-up time before they can be used incertain applications and may have a similar shut-off period. Often, thelaser itself may be a far more sophisticated piece of equipment than isactually required for a particular task and therefore may be over suitedto the task in hand. Some medical applications do not in fact requirethe criticality offered by a laser although other acceptable lightsources do not seem to have been developed to be used instead of a laserin such applications.

Non-laser light sources have been developed for medical applications butsuch proposals have tended to be inefficient and generally unsuitablefor the task in hand. For example, a paper from the Journal ofPhotochemistry and Photobiology B: Biology 6 (1990) 143-148 onPhotodynamic Therapy with Endogenous Protoporphyrin reports the use of a500 watt filament light source for irradiation of cancerous cells. Thelight source was varied from 150 to 300 watts per square centimeter butspread over a very wasteful large bandwidth greater than 100 nm. Thefiltering tended to be inefficient and unsuitable giving rise to tissuedamage from thermal effects.

Another proposal is discussed in the “Phototherapy of Human Cancers” inan article entitle Porphyrin Localisation and Treatment of Tumors, pages693-708, 1994 Alan R. Liss, Inc. This article discusses the use of afiltered incandescent lamp having a 1000 watt filament source which iswater cooled. The size of the apparatus itself is large and tends to beinefficient also entailing considerable risk of skin damage because ofhigh flux density.

It is an object of at least some embodiments of the present invention toprovide an incoherent or non-laser light source which at leastalleviates one or more of the aforementioned, or other, disadvantagesassociated with lasers or which is more suited to the particular task inhand than a laser.

According to a first aspect of the present invention there is providedan incoherent or non-laser light source comprising a high intensitylamp, a bandpass filter and focusing means arranged to yield a lightbeam having an output intensity greater than 0.075 watts per squarecentimeter for a bandwidth in the range 0 to 30 nm and preferably in therange 0 to 25 nm.

Usually, the output intensity of said light source will be greater than1 watt per square centimeter for a bandwidth usually in the range 20 to25 nm.

Preferably, the light source is tunable over a range of at least 350 to700 nm and usually over a range of 250 to 1100 nm.

Preferably, the output beam is focused sufficiently so that light can bedelivered by way of an optical fibre means or bundle to its point ofaction and said beam may be focused down to a 6 mm or less diameter.

In one embodiment of the present invention, the light source may bearranged to yield a beam with an output intensity of 6 watts per squarecentimeter at a bandwidth of 20 to 25 nm. The lamp may be a metal halidelamp.

Alternatively, the lamp may be a high intensity high pressure xenon,short arc lamp or any lamp producing intense light over a continuousspectrum. It is envisaged that an extended light source such as afilament would not produce the required intensity due to filamentdiversions. In this context a short arc lamp would appear to be the bestoption yet available and may be for example of only 300 watts or 500watts, but preferably less than 1 kw due to heat output and and arclength. Preferably, the beam divergence of the lamp is very low, forexample in the order of 4° FWHM with a beam stability preferably in theorder of 1%. Preferably, the lamp is adapted (for example by coatingvarious parts thereof) to remove ultra-violet (UV) radiation from thelight beam emerging from a lamp window.

The focusing means, preferably, comprises an aspheric lens and said lensis preferably anti-reflection coated.

The bandpass filter may be at least 50% or 65% efficient and ispreferably 80% efficient or greater (e.g. 91%) for light within thetransmission bandwidth.

A dichroic “hot mirror” may be provided to remove infra-red radiationfrom the beam.

A variable attenuator grill may be provided in order to vary the poweroutput of the light source.

The light source is, preferably, provided with a readily interchangeableoutput window incorporating a connection matching a connection on afibre optic bundle. In this manner the window can be interchanged forone having a different sized connection for a different sized fibreoptic bundle. The output window may be provided in a screw cap.

A preferable embodiment of the present invention provides a portablelight source. The size of the light source may have overall dimensionsof 15″ by 10″ by 6″. The light source may be provided with a powersupply connected to the lamp (preferably a xenon arc lamp or metalhalide lamp). A cooling fan is preferably provided at the rear of thelamp. The light source may comprise a control shutter positioneddirectly in front of the lamp (in an alternative arrangement the shuttermay be provided in between the bandpass filter and the aspheric lens)and followed by a dichroic “hot mirror” or other means to removeinfra-red radiation and then by the bandpass filter, aspheric focusinglens and variable attenuation means. The light source is preferablyprovided with a control panel at the front thereof in order to operatethe control shutter for timed exposure as well as perhaps incorporatingmanual override switches. The light source is, preferably, tunable byreplacement of the bandpass filter and/or dichroic “hot mirror”. If itis desired for the emergent beam to be in the infra-red region forexample for treatment of hyperthermia the “hot mirror” can be replacedwith a cold mirror to filter out the visible light. Additionally, thebandpass filter may be changed for one allowing light of a greaterbandwidth (for example, 100 or 200 nm) to pass through.

Further according to the present invention there is provided a non-laserlight source comprising one or more of the following features:

(a) means for supplying a (monochromatic) light beam suitable fordelivery into a fibre optic bundle, said light beam having a sufficientintensity for a bandwidth useful in PDT (photodynamic therapy) and/or incosmetic methods of dermatological treatment,

(b) means for supplying a light beam of an intensity of at least 100 mwper square centimeter for a bandwidth in the range 20 to 25 nm,

(c) means for providing a beam of intensity greater than 0.075 watts persquare centimeter which is tunable in the range of 250 to 1100 nm,

(d) said light source being portable and air cooled,

(e) means for delivering a (monochromatic) light beam to fibre opticbundles having different connector sizes,

(f) a bandpass filter of 60 to 90% efficiency or greater in a narrownanometer range (for example less than 25 nm),

(g) facility for interchanging bandpass filters of differentcharacteristics,

(h) said non-laser light source being suitable for medical applicationsin particular treatment of tumours and/or delivery of light suitable forphoto-inactivation of cancer cells containing a drug having anabsorption level in a narrow nanometer bandwidth, for example lying inthe range 20 to 25 nm.

Further according to the present invention there is provided a method ofin vitro PDT, said method comprising delivering non-laser light of asufficient intensity to kill cancer cells, preferably of an intensitygreater than 0.075 W/cm² and usually 10 to 200 mW/cm² for a bandwidth inthe range 20 to 25 nm.

Further according to the present invention there is provided a cosmeticmethod of treatment of dermatological conditions, for example comprisingremoval of portwine stains, tattoos or psoriasis, using an incoherentlight beam from a non-laser light source emitting a high intensity beamhaving an intensity greater than 0.075 watts per square centimeter for abandwidth in the range 0 to 25 nm, said beam preferably beingdeliverable by an optic fibre bundle, and said method preferablycomprising pulsing said beam. For removal of portwine stains wavelengthsof 575 nm may be used and for removal of tattoos wavelengths of 620 nmmay be used. The method may involve the introduction of a drug into thebody undergoing cosmetic treatment, said drug being selectivelyactivated by light of a particular wavelength.

According to a further aspect of the present invention there isprovided, a non-laser light source suitable for medical applications,which source is tunable over a bandwidth of 350 to 700 nm (preferablyover a bandwidth of 250 to 1100 nm) and which is capable of focusing alight beam for fibre optic delivery at an intensity of 100 mW/cm² for abandwidth of 25 nm or less.

Preferably, said light source is capable of focusing a beam at anintensity of up to 9 W/cm² for a bandwidth of 25 nm or less.

Usually, the light source will be provided with a timed exposurefacility and it is advantageous for the beam to be as intense aspossible below thermal dosage and hyperthermia limits (a few 100 mw/cm²)since this will reduce the exposure time required.

An embodiment of a light source in accordance with the present inventionwill now be described by way of example only, with reference to theaccompanying drawings in which:

FIG. 1 shows a much simplified schematic over view of the light source;

FIGS. 2 a, 2 b, 2 c show graphical data related to in vitro work, and

FIGS. 3 a, 3 b show test results of the Applicant related to in vitrowork.

The FIGURE shows a high intensity incoherent or non-laser light source 1in schematic form. Light source 1 includes a lamp 2 which may be a highintensity, high pressure, xenon, short arc lamp (for example of 300 or500 watts output) which would normally produce broadband ultra-violet,visible and infra-red radiation. Such a lamp has a beam divergence inthe order of 4° FWHM and a beam stability in the order of 1%. Such alamp is marketed by ILC Technology of Sunnyvale, Canada. In thisembodiment the lamp 2 is provided with a rear internal lamp reflector(not shown) and has a front window 2 a which is a single crystal,sapphire window. The reflector and window 2 a are provided with coatingsselected to remove ultra-violet radiation from the emergent light beamfrom the window 2 a. Removal of the ultra-violet radiation preventsharmful ozone production. The xenon lamp 2 is provided with othervarious components of the light source in an exterior casing 3 providedwith a front control panel 4. A power supply unit 5 is provided to powerthe lamp 2 via electrical connection 2 c and a rear cooling fan unit 6is provided to cool the whole apparatus 1. A solenoid activated controlshutter 7 is provided in front of the window 2 a of the lamp and thiscontrol shutter is activated by a suitable control switch (not shown)provided on the control panel 4, said control shutter 7 being connectedthereto by way of electrical connection 7 a. Thus, the control shuttercan be activated so that the light source can administer timed doses of0 to 9999 seconds covering all medical exposures required. Manualoperation and a manual override to terminate a time exposure is alsoprovided in the light source 1 which is operable from the control panel4. The control shutter 7 is operated by an inbuilt special purposetimer/controller.

In this embodiment of the apparatus 1, a Dichroic “hot mirror” 8 ispositioned in front of the control shutter 7 in the beam path and thisacts to remove infra-red radiation from the beam passed by the controlshutter 7 resulting in a relatively smooth visible broadband beam in therange of 350 to 700 bandwidth at 50 mW/nm. The emergent beam from the“hot mirror” 8 impinges next upon a dielectrically blocked, hightemperature bandpass filter 9 which selectively filters the light beamto produce an emergent beam of a much narrower bandwidth, preferably, inthe order of 20 to 25 nm. Most importantly, in this example the bandpassfilter is 80% efficient at filtering the light lying in said bandwidthin order to enable a sufficiently intense beam to be produced by thelight source 1 which is suitable for various medical applications. Sucha bandpass filter may be obtained from Omega Optical c/o Glen Spectra inMiddlesex.

The beam emergent from the bandpass filter is in the order of 2 to 2.5cm diameter and is then focused by an anti-reflection coated F1 asphericlens 10 which focuses the beam down to about 6 mm diameter at the outputwindow 11 of the light source 1. The coating itself may be a magnesiumfluoride coating which reduces losses of for example 10 to 15% down toonly 3% in energy of the beam. The lens 10 is a tight variable anglelens and can be obtained from Ealing Electro-Optics of Watford.

A variable attenuator means in the form of grill 12 is provided, saidgrill being a plate which is rotatable about its own axis in order tovary the intensity of the output beam. Areas of the plate are providedwith apertures (not shown) graduated in size according to the angle towhich the plate is rotated to allow more or less of the beam through inorder to vary the power of the output beam between zero and full power.Such a method of varying the power output of the output beam ispreferable to using a control on the lamp 2 itself and should extend theworking life of the lamp.

The output window 11 is provided in a screw-cap 13 which can be fittedinto the bulkhead 14 of the light source 1. The screw-cap 13 is providedwith a central tubular aperture matched to the connection end 15 a of anoptical fibre bundle 15 of 5 mm or less diameter and of 1 to 4 meters orgreater in length. Thus, the lens 10 is designed to minimise opticallosses and spherical abberation and focus the beam sufficiently toenable delivery of the light to its point of action by way of an opticalfibre bundle. Such a fibre bundle may be obtained from Eurotec OpticalFibres, Doncaster.

It is envisaged that the light source as described will be invaluable inall types of medical applications where hitherto only a laser has beenavailable. In particular the light source (which may be thought of asmimicking a laser) as shown in self-contained and portable, the externaldimensions of the casing being in the order of 15″ by 10″ by 6″, saidlight source being lightweight and robust unlike lasers required forsimilar medical applications. Additionally, the light source requires avery low electricity consumption particularly in comparison with alaser.

The light source 1 as shown in the FIGURE can be arranged to yield abeam output from the cap 13 having an intensity of 3 watts per squarecentimeter for a bandwidth of 20 to 25 nm and if the xenon lamp 2 isreplaced by a metal halide lamp it is believed that a beam intensity of9 watts per square centimeter can be achieved for the same bandwidth.Delivery of light from the light source 1 to the point of action may beby way of the fibre bundle 15 and there may be considerable losses inintensity of the beam down the optical fibre bundle perhaps in the orderof 50%. Losses can be improved by the choice of fibre bundle. In anyevent, the intensity of light delivered by the light source as describedat the distal tip of the fibre bundle 15 may be in the order of 30 to 40m Watts per nanometer over a bandwidth of 20 to 25 nm and this has beenproven very effective in certain medical applications where a laserwould be required. For example, in the area of photodynamic therapy(PDT) there has been proven photo-inactivation of cancerous ChineseHamster Ovary (CHO) cells in vitro with the haematoporhyrin derivativeHpD with impinging light on the cells being in the visible band at630±12 nm. Test results have indicated a similar cell kill efficiencyand quality of kill to that achieved by current medical lasers.Accordingly, some results obtained by the Applicant will now bediscussed with reference to FIGS. 2 a to 2 c and 3 a, 3 b.

IN VITRO PDT TEST RESULTS

In vitro work carried out using Chinese hamster ovary (CHO) cellsincubated with 10 pg/ml HpD for 24 hours. Irradiation was centred on630±12 nm for three light sources, namely a high intensity continuouswave (CW) lamp (non-laser light source in accordance with the presentinvention using 300 W Xenon lamp), secondly a continuous wave 20 W argonion pumped dye laser and pulsed 10 W copper vapour pumped dye laser, allthe fibre delivery. Light doses ranged from 0 to 2.5 J/cm² with lightfluences ranging from 20 to 200 mW/cm². A light only control was takenat 275 mW/cm² for energy doses of 0 to 100 J/cm². Following irradiation,cells were plated out, stained and counted for survival.

FIGS. 2 a, 2 b, 2 c show photosensitiser (HpD) absorption spectrum, cellkill efficacy spectrum and overlapping HpD/lamp spectra. PBS refers tophosphate buffered saline; S.F. means survival fraction.

FIGS. 3 a, 3 b show cell survival curves obtained at 20 & 50 mW/cm²respectively with highest kill efficiency achieved by the argon ionlaser, followed by the copper vapour laser. The lamp kill efficiency ofthe light source in accordance with the present invention, thoughsimilar to the lasers (approx 70%) would be increased by reducing itsemission bandwidth from 30 nm.

In PDT a drug (such as HpD) is introduced into cancerous cells, whichdrug absorbs light in a narrow bandwidth (for example 20 to 25 nm) onlyand the light source is set up to emit a beam only in that requiredbandwidth which for HpD is 630±12 nm. Other drugs only absorb light ofdifferent wavelengths but once again in a narrow bandwidth and it is aneasy matter to arrange for the light source to emit light at a differentwavelength but still within the same narrow bandwidth merely by changingthe bandpass filter 9. In the arrangement as shown, the bandpass filter9 would have to be removed from the light source and a new one insertedin its place but in a modification it is possible that multiple bandpassfilters could be incorporated into a movable frame (for example arotatable disc) in order for a different bandpass filter filtering outlight of a different wavelength (but within the same narrow bandwidth ifrequired) to be quickly and easily presented in the beam path.

In fact, the drug HpD has further selective absorption bands atdifferent bandwidths and different bandpass filters can be matched tothese bandwidths. For example, HpD has an absorption band in the blueregion and in the U.V. region at about 400 nm and at about 500, 540 and570 nm. However, the shorter the wavelength the less the penetration.More efficient blue light could be used for typographical ordermatological work (penetration approximately 1 to 2 mm).

However, for large tumours or interstitial work 5 to 10 mm penetrationis usually required and therefore light of longer wavelength isrequired.

Most importantly, the selection of a suitable bandpass filter from arange of bandpass filters provides a unique tuning facility for thelight source. This feature itself is a very significant advantage overlasers which are set to emit light of one wavelength only and do nothave such a tuning capacity. Thus, different medical lasers are requiredfor different medical applications where different wavelengths of lightare required. With the light source 1 in accordance with the presentinvention the same piece of apparatus can be used for different medicalapplications requiring different wavelengths of light to be employed(merely by changing the bandpass filter), once again providing anenormous cost advantage and convenience over medical lasers.

Thus, the light source 1 can provide variable bandwidth opticalemissions centred on any wavelengths from 250 nm to 1100 nm deliverableby optical fibre of sufficient intensity to initiate either in vitro orin vivo external/interstitial photodynamic therapy (PDT). If it isdesired to deliver light outside of the visible region i.e. in theinfra-red region between 700 nm and 1100 nm or so this can be done bythe light source 1 merely by changing the dichroic mirror 8 for a coldmirror which blocks the visible light but allows a light through in thebandwidth region 700 to 1100 nm. Therefore, the tunability of the lightsource extends to the infra-red for Hyperthermia applications. Light oflonger wavelength is generally required for such applications since abetter penetration can be achieved but a narrow bandwidth is not usuallyrequired. The bandwidth may be 200 or even 300 nm.

Overall, the light source 1 can be used used in selective drugactivation and the effective monochromaticity of the output enables:

1. selection of biochemical absorption bands

2. selective targeting of tissue

3. variation of optical penetration.

It is envisaged that the light source 1 could be developed formonofilament fibre delivery to treat internal carcinomas with PDT andthe output of the light source could be pulsed to minimise thermaleffects for treatment of Portwine stains and tattoos.

In summary, the present invention provides a high intensity incoherentlight source which combines the advantages of a laser (i.e. directionalmonochromatic and intense beam) with the advantages of lamp technology(i.e. low costs, simple design with reliability and a very broad tuningrange). Thus, a portable device can be constructed which includes afibre optic delivery system, said device being useful in a wide range ofapplications, in particular medical applications (both medical andtherapeutic) such as in photodynamic therapy, hyperthermia,dermatological treatment such as removal of portwine and tattoo stains.Additionally, it is possible that the unit could be utilised in the areaof diagnostics, although it has not been developed primarily for this.Thus, the present invention provides a light source yielding sufficientpower within a narrow bandwidth suitable for PDT in addition torendering the light deliverable via an optical fibre.

The fibre bundle 15 may be arranged to deliver a ½ watt of light withsteep-sides 25 nm FWHM bandwidth to a patient directly or via a specialpurpose 2-lens collimating/focusing beamprobes or light conduits.

The output power of the light source will usually be at least in theorder of 100 mW/cm².

Still further according to the present invention there is provided ahigh intensity incoherent or non-laser light source comprising a lamp, a(bandpass) filter and focusing means arranged to yield a monochromaticoutput beam of intensity greater than 0.075 watts per square centimeterwhich is tunable in the range of 250 to 1100 nm and which is preferablydeliverable by a fibre optic bundle to a point of action.

It is to be understood that the scope of the present invention is not tobe unduly limited by the particular choice of terminology and that aspecific term may be replaced by any equivalent or generic term. Furtherit is to be understood that individual features, method or functionsrelated to light source might be individually patentably inventive. Inparticular, any disclosure in this specification of a range for avariable or parameter shall be taken to include a disclosure of anyselectable or derivable sub-range within that range and shall be takento include a disclosure of any value for the variable or parameter lyingwithin or at an end of the range. The singular may include the pluraland vice versa.

What is claimed is:
 1. A cosmetic method of treatment of dermatologicalconditions, comprising the introduction of a drug into a body undergoingsaid cosmetic treatment, said drug being selectively activated by lightof a particular wavelength, and irradiating an affected area of the bodywith an incoherent high intensity non-laser light beam of saidwavelength.
 2. A cosmetic method of treatment of dermatologicalconditions, comprising irradiating the affected area with an incoherenthigh intensity non-laser light beam having an intensity greater than0.075 watts per square centimeter, said light beam having only abandwidth in the range 0 to 30 nm.
 3. A method as claimed in claim 2, inwhich said beam is delivered to the affected area by optic fiber.
 4. Amethod as claimed in claim 2, comprising pulsing said beam.
 5. A methodas claimed in claim 2, for removal of portwine stains.
 6. A method asclaimed in claim 2, for removal of tattoos.
 7. A method as claimed inclaim 2, comprising the introduction of a drug into the body undergoingcosmetic treatment, said drug being selectively activated by light of aparticular wavelength.
 8. A method as claimed in claim 2, in which thelight beam is a continuous wave.
 9. A method as claimed in claim 2, forremoval of psoriasis.
 10. A method as claimed in claim 2, wherein thebeam has an intensity greater than 0.075 watts per square centimeter fora bandwidth in the range 0 to 25 nm.
 11. A method as claimed in claim 5,in which a wavelength of 575 nm is used to remove portwine stains.
 12. Amethod as claimed in claim 6, in which a wavelength of 620 nm is used toremove tattoos.